Electrochimica Acta 162 (2015) 198–204

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Electrochimica Acta
journal homepage: www.elsevier.com/locate/electacta

Sensitive Detection of Acetaminophen with Graphene-Based

Electrochemical Sensor
Bal-Ram Adhikari, Maduraiveeran Govindhan, Aicheng Chen * ,1
Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay Ontario P7B 5E1, Canada

A R T I C L E I N F O A B S T R A C T

Article history: Here we report on a high-performance electrochemical sensor for the sensitive detection of
Received 7 August 2014 acetaminophen based on graphene, which was simultaneously electrochemically reduced and deposited
Received in revised form 8 October 2014 onto a glassy carbon electrode (GCE). The electrocatalytic properties of the electrochemically reduced
Accepted 9 October 2014
graphene (ERG) toward the oxidation of acetaminophen were analyzed via cyclic voltammetry (CV),
Available online 13 October 2014
differential pulse voltammetry (DPV) and chronoamperometry. For comparison, various ERG/GCEs were
prepared with different electrodeposition cycles to optimize the amount of the ERG. Our experimental
Keywords:
results showed that the optimized ERG/GCE possessed robust activity in the electrochemical oxidation of
Graphene
Acetaminophen
acetaminophen, leading to the development of highly sensitive electrochemical sensor for its detection.
Differential pulse voltammetry An extremely low detection limit of 2.13 nM and a wide linear detection range of from 5.0 nM to 800 mM
Amperometry were achieved via the combination of the amperometric technique and DPV. The developed
Electrochemical sensor electrochemical sensor was further employed for the determination of acetaminophen in human
serum, with excellent recovery, ranging from 96.08% to103.2%. The fabricated electrochemical sensor also
demonstrated high selectivity, stability and reproducibility. The wide linear detection range obtained in
this study for the detection of acetaminophen showed strong potential as a promising sensing technique
for pharmaceuticals, in terms of quality control and in clinical laboratories for acetaminophen as relates
to the determination of hepatotoxicity.
ã 2014 Elsevier Ltd. All rights reserved.

1. Introduction Approximately 30–35% of acetaminophen metabolism occurs via

Acetaminophen, having the chemical name N-acetyl-p-amino-
phenol (APAP), is a widely utilized analgesic pain reliever and fever
reducer [1,2]. It is considered to be safe when administered at
recommended dosages; however, it can cause hepatotoxicity
at higher doses [3]. Following oral ingestion, acetaminophen is
rapidly absorbed and metabolized, primarily in the liver, to achieve
peak plasma levels within 1 h. Plasma concentrations during
therapy typically range from 2 to 20 mg/L, whereas levels of
30–300 mg/L are often observed in overdosed patients [4,5]. The
principle routes of elimination are glucuronidation and sulfation,
although oxidation may also occur [6].
Glucuronidation is the primary route of elimination in human
adults, accounting for about 45–55% of an acetaminophen
dose [6,7]. This step may be catalyzed by a series of uridine
diphosphate glucuronyl transferase (UGT) enzymes such as
UGT1A1, UGT1A6, UGT1A9, and UGT2B15 in the liver [7–10].
* Corresponding author. Tel.: +1 807 3438318
E-mail address: aicheng.chen@lakeheadu.ca (A. Chen).
1
ISE active member
sulfation. In the adult human liver this is catalyzed by SULT1A1,
SULT1A3, SULT1A4, SULT1E1 and SULT2A1 [11–13]. The
bioactivation of acetaminophen in the formation of N-acetyl-p-
benzoquinone imine (NAPQI) is carried out via the CYP450 family
of enzymes [6], which are toxic metabolites that are responsible
for hepatotoxicity. The toxic metabolite, NAPQI, is initially
detoxified by glutathione conjugation within the liver, and
subsequently by acetylation in the kidneys, followed by N-acetyl
transferase catalyzation, and final excretion in the urine [8]. In
cases of overdose the accumulation of NAPQI is high, which
causes adverse side effects.
The development of a simple, rapid, sensitive and accurate
analytical technique for the determination of acetaminophen in
pharmaceuticals and in clinical preparations is indeed warranted.
Various methods, such as titrametry [14,15], spectrophotometry
[16,17], HPLC [18,19], chemililuminescence [20], have been
developed for the determination of acetaminophen in pharma-
ceutical tablets and biological fluids. However, titrametric,
spectrophotometric and chemiluminescence methods involve
tedious extraction processes prior to detection. Additionally, liquid
chromatography is time consuming, which makes it unsuitable for
the analysis of acetaminophen in practice [21]. On the other hand,

http://dx.doi.org/10.1016/j.electacta.2014.10.028
0013-4686/ ã 2014 Elsevier Ltd. All rights reserved.
 B.-R. Adhikari et al. / Electrochimica Acta 162 (2015) 198–204
electrochemistry provides powerful analytical techniques with
advantages of instrumental simplicity, moderate cost and
portability [22]. Since most electroanalytic techniques are selec-
tive and capable of highly sensitive and rapid measurements over a
wide linear range, which require no sample preparation, and given
the fact that acetaminophen is electroactive; electrochemical
techniques may be considered as viable and improved alternatives
for the determination of acetaminophen over other methods [23].
Since nanomaterials exhibit unique mechanical, electrical,
electronic, optical, magnetic, surface and biological properties,
which are not found in conventional bulk materials, they have a
great potential utility in analytical chemistry for sensor modifica-
tion [24,25]. Graphene has recently attracted tremendous interest
due to its exceptional thermal, mechanical, and electronic
properties [26], thus one of its many promising applications lies
in the development of electrochemical sensors [27,28]. Single
carbon atom thick graphene sheets provide extremely high surface
areas with readily available access to surface resident atom
populations for electron transport, which impart a high sensitivity
to adsorbed molecules [29]. Due to the unique properties of
graphene, when it is utilized for the modification of bare
electrodes, it has great potential for distinguishing a diverse range
of organic compounds. To date, the deposition of graphene films on
electrodes has typically been achieved via drop-casting solution-
based graphene, which is derived from the chemical reduction of
graphene oxide (GO) sheets [30]. However, these methodologies
have intrinsic limitations such as a lack of control over film
thickness and most importantly, toxic chemicals are involved. Most
recently, the electrochemical reduction of GO to graphene has
garnered considerable attention due to its rapid and green nature
[31–35]. The excellent conductivity, high surface area, and oxygen-
related defects of ERG films make them a sensitive promoter of
electrochemical sensing processes [36–38].
The objective of this work was to establish a convenient,
cost-effective and highly sensitive method for the determination of
acetaminophen in pharmaceutical formulations and human bodily
fluids based on the ERG/GCE. In the present study, the electro-
chemical oxidation of acetaminophen on electrochemically
reduced graphene (ERG)-modified glassy carbon electrodes (GCEs)
was investigated, leading to the development of a high-perfor-
mance electrochemical sensor for the analysis of acetaminophen,
with an extremely low detection limit and a wide linear detection
range. In addition, the electrochemical sensor developed in this
study was successfully employed for the detection of acetamino-
phen in human serum and pharmaceutical samples, demonstrat-
ing that the proposed electrochemical sensor has strong potential
for practical utility in clinical and quality control laboratories, as
well for therapeutic drug monitoring and hepatotoxic serum level
determination in hospital laboratories.
2. Experimental
2.1. Apparatus
All electrochemical experiments, including cyclic voltammetry
(CV), differential pulse voltammetry (DPV) and amperometry
were performed with a CHI 660 electrochemical workstation (CH
Instruments Inc. USA) using a conventional three-electrode system
that consisted of a platinum coil counter electrode, a Ag/AgCl (3 M
KCl) reference electrode, and a working electrode, which was
comprised of 3 mm in diameter (modified and unmodified) glassy
carbon electrodes (GCEs). A field-emission scanning electron
microscope (FE-SEM) (Hitachi SU-70) was utilized for the character-
ization of the graphene-modified GCE surface. All experiments were
performed at room temperature, 20  2  C, and the electrode
potentials quoted are versus an Ag/AgCl electrode.
199
2.2. Chemicals and reagents
Acetaminophen (AP), graphene oxide (GO) dispersed in water
(2 mg/mL), and human serum (from human male AB Plasma) were
purchased from Sigma-Aldrich. Generic tablets (350 mg each,
containing 325 mg acetaminophen) were obtained from the
Thunder Bay Regional Health Sciences Center pharmacy. All other
reagents were of analytical grade and utilized as supplied. All
solutions were prepared with pure water (18.2 MV cm), which was
generated by a Nanopure1 water purification system. All acetamin-
ophen solutions were freshly prepared and used within 24 h.
2.3. Electrode fabrication
Prior to modification, a glassy carbon electrode (GCE) was
polished with 0.05 mm alumina powders, subsequently sonicated
in pure water, and allowed to dry at room temperature. To produce
the ERG, a 2 mg/mL GO solution was added to a 0.067 M pH
7.4 phosphate buffer solution (PBS) via homogenous mixing, to
form a 0.3 mg/mL GO colloidal dispersion. The GO suspension in
the electrochemical cell was deoxygenated using Ar gas for 15 min.
Simultaneous electrochemical reduction and deposition of
graphene on the GCE were performed in the GO suspension
(0.3 mg/mL) in the electrode potential range between -1.5 and 0.5 V
at a sweep rate of 10 mV/s. The resulting ERG/GCE was cleaned
with pure water, and then dried at room temperature for 1 h.
2.4. Electrochemical measurements
Electrochemically reduced graphene modified glassy carbon
electrodes were used as working electrodes in a three-electrode
electrochemical cell. A stock solution of 0.01 M acetaminophen
was prepared, where after a calculated amount of stock solution
was added to 20 mL of 0.1 M phosphate buffer solution (PBS) at pH
7.4 to obtain the desired concentration of acetaminophen. The
experiments were carried out by studying the cyclic voltammetric
behavior of the acetaminophen at a potential range of from 0.0
to 0.6 V. The DPV was performed at potential range of from 0.0 V to
0.6 V, with a pulse width of 0.2 s, pulse period of 0.5 s and potential
increment of 4 mV. All amperometric measurements were
acquired at 0.5 V with continuous magnetic stirring in order to
maintain a homogeneous concentration.
2.5. Determination of pharmaceutical samples in human serum
The developed sensor was tested for the determination of
acetaminophen using the generic acetaminophen tablets in human
serum. Prior to conducting the experiment, the human serum
sample had been stored in a freezer. The tablets were weighed,
ground into a powder, and then dissolved in 5 mL of human serum
samples to obtain a 0.01 M stock solution concentration. The
solution was further treated with acetonitrile for protein
precipitation and then sonicated for 5 min. The acetaminophen/
human serum solution was then centrifuged at 4000 rpm for
15 min in order to remove any protein residues. The supernatant
was subsequently collected and diluted to obtain 10–25 mM
concentrations of acetaminophen in 0.1 M PBS. The recovery
tests were carried out using DPV for the determination of
acetaminophen in human serum.
3. Result and Discussion
3.1. Surface and electrochemical characterization of the ERG/GCE
Fig. 1A presents the 1st (blue), 3rd (green) and 5th (red) cycle of
the cyclic voltammograms (CVs) during the simultaneous
200 B.-R. Adhikari et al. / Electrochimica Acta 162 (2015) 198–204

electrochemical reduction and deposition of graphene on a GCE

surface in 0.3 mg mL 1 GO dispersed in a 0.1 M phosphate buffer
solution (PBS). Increasing the number of scans from the first to fifth
cycles, the oxidation peak at around 0.0 V shifted to more positive
potential and became broader; the double layer capacitance was
also increased, indicating more electrochemical reduced graphene
(ERG) was deposited on the GCE. FE-SEM was employed to study
the surface characteristics and morphology of the ERG modified
GCE. The SEM image presented in Fig. 1B confirmed the existence
of uniformly covered ERG on the GCE surface.
Fig. 2 presents the CVs of the ERG/GCEs recorded in a 0.1 M PBS
(pH 7.4) at a sweep rate of 20 mV/s in the absence (red dashed
curve) and in the presence of 250 mM acetaminophen (red solid
curve). For comparison, the CVs of a bare GCE recorded in a 0.1 M
PBS (blue dashed line) and after the addition of 250 mM
acetaminophen solution (blue solid line) are also displayed in
Fig. 2. As expected, no oxidation and reduction peaks appeared for
both the bare GCE and the ERG/GCE in the PBS at the applied
potential range. However, the double-layer capacitance of the GCE
was significantly increased after the ERG deposition. In the
presence of acetaminophen, a broad peak appeared at  +0.5 V
for the bare GCE, which can be attributed to the electrochemical
oxidation of acetaminophen; however, no reduction peak was
observed in the investigated potential range, indicating a slow rate
of electron transfer occurred at the bare GCE, resulting in an
irreversible oxidation process. In contrast, for the ERG/GCE, a pair
of strong and well-defined redox peaks was observed with Epa at
387 mV and Epc at 316 mV, showing that the fabricated ERG/GCE
favours the reversible electrochemical reaction, as illustrated in
the scheme below:
Fig. 1. (A) CVs (the 1st, 3rd and 5th cycle) of a glassy carbon electrode (GCE) recorded
in 0.1 M PBS (pH 7.4) containing 0.3 mg mL 1 GO at a scan rate of 10 m Vs 1. (B) SEM
image of the GCE modified with electrochemical reduced graphene (ERG).

which were prepared with two, five and ten electrodeposition

where two electrons and two protons are involved in the
oxidation and reduction process. The significant increase in
the peak currents and the well-defined redox peaks show that
the ERG/GCE not only had a high electrochemical active surface
area, but also possessed excellent electrocatalytic activity, which
are desirable attributes for the development of electrochemical
biosensors.
We also studied the effect of the scan rate on the electrochemi-
cal oxidation and reduction of acetaminophen at the ERG/GCE.
Fig. 3A displays the CVs recorded in a 0.1 M PBS + 250 mM
acetaminophen solution at different scan rates (20, 50, 75,
100 and 125 mV/s). The Epa was only slightly shifted to positive
potentials, while the Epc was negatively shifted marginally, further
confirming the rapid charge-transfer kinetics of the produced ERG.
Fig. 3B presents the plots of anodic peak current (IPa) as well as the
cycles, as described in Section 2.3, which was recorded in a 0.1 M
PBS (pH7.4) containing 250 mM acetaminophen. When increasing
the electrodeposition, from two cycles (Curve a) to five cycles
(Curve b), (i) the background current was increased from 2.5
to 5.0 mA, showing that the electrochemical active surface area/
double-layer capacitance was doubled; (ii) the peak potential was
negatively shifted from 385 to 370 mV, indicating the catalytic
activity of the formed ERG was enhanced; and (iii) the current
response to acetaminophen was also significantly increased, from
9.5 to 17.5 mA. However, a further increase of the
10
8
6
4
I / μΑ

cathodic peak current (IPc) versus the square root of scan rate (v1/2).
2
The obtained linear relationship with high correlation coefficient
R2 (0.998 for the cathodic peak current and 0.999 for the anodic 0
peak current) indicates that the electrochemical oxidation
and reduction of acetaminophen were a diffusion-controlled -2
process [39].
-4

0.1 0.2 0.3 0.4 0.5 0.6

3.2. Effect of electrodeposition cycles
The influence of the electrochemical deposition cycles on the
behavior of the resulting ERG/GCE was also investigated using DPV.
Fig. 4 presents the DPV curves of three different modified GCEs,
E vs (Ag/AgCl) / V
Fig. 2. CVs of the bare GCE (blue curves) and the ERG/GCE (red curves) recorded in
0.1 M PBS (pH 7.4) in the absence (dashed lines) and in the presence of 250 mM
acetaminophen (solid lines) in 0.1 M PBS at a scan rate of 20 mV s 1.
 B.-R. Adhikari et al. / Electrochimica Acta 162 (2015) 198–204 201

electrodeposition, from 5 to 10 cycles (Curve c) resulted in a
positive shift of the peak potential and a decrease of the current
response to acetaminophen, revealing that a thicker ERG coating
could inhibit electron transfer and decrease the electrocatalytic
activity. Consequently, five electrodeposition cycles were
employed to fabricate the ERG/GCEs for the detection of
acetaminophen. In addition, a comparison of the CV (red solid
curve) in Fig. 2 and the DPV curve b in Fig. 4 revealed that the
current response to acetaminophen of the ERG/GCE was over twice
as high as when measurements were carried out using DPV,
indicating that DPV is a superior technique than CV for the
detection of acetaminophen as expected.
3.3. Acetaminophen detection using DPV
Fig. 5A displays a series of the DPV curves of the ERG/GCE
recorded in a 0.1 M PBS containing n mM acetaminophen, where n
was varied from 0.0 to 800. The concentration was increased at
10 and 100-mM intervals when n  45 and n  100, respectively.
For clarification, the DPV curves with the acetaminophen
concentration, changing from 0.0 to 45 mM, are enlarged and
presented as an insert in Fig. 5A. The small pre-peak (shoulder)
observed in the potential range between 0.2 and 0.3 V might be
attributed to the initial adsorption of acetaminophen prior to the
electrochemical oxidation on the electrode surface. The current
response was observed to be linearly elevated with the increase of
acetaminophen concentrations. The calibration plot of the current
response of the ERG/GCE versus the acetaminophen concentration
is presented in Fig. 5B, showing a very good linear relationship,
40
A 125 mVs-1
30
20
I/ μΑ
with the correlation coefficient R2 = 0.996. The limit of detection
(LOD) was calculated to be 1.2 mM using 3s/b, where s is the
standard deviation of the blank and b is the slope of the calibration
curve. According to the acetaminophen nomogram (plot of
acetaminophen serum concentration against time), a serum
plasma concentration of higher than 700 mM at four-hours, or
higher than 160 mM at twelve-hours post-ingestion of acetamino-
phen tablets, is considered as hepatotoxicity [40,41]. Thus, the
wide linear detection range (5–800 mM) of DPV enabled by the
ERG/GCE might be utilized for the detection of acetaminophen
serum levels of overdosed patients.
3.4. Acetaminophen detection via amperometry
During the pharmaceutical formulation, as well as quality
control testing of acetaminophen products, a lower than 5 mM
measurable detection limit is required. The analytical performance
of the ERG/GCE, challenged with low acetaminophen concen-
trations (5 nM to 4 mM), was evaluated utilizing the amperometric
technique. The effect of the applied electrode potential on the
amperometric response to acetaminophen was investigated at
different potentials (0.40, 0.45, 0.50, 0.55 and 0.60 V), showing that
the current response was increased when the potential was
elevated to 0.5 V. However, the current response remained almost
the same with further increases of the electrode potential, to
0.55 and 0.60 V. Thus 0.50 V was selected for the amperometric
detection. Fig. 6A depicts the amperometric response of the
ERG/GCE at the applied constant electrode potential of 0.5 V to the
addition of acetaminophen in a 0.1 M PBS. A rapid increment of
current was observed upon the successive addition of 5 nM (first
segment), 0.2 mM (second segment) and 2 mM acetaminophen
(third segment). For clarification, the initial segment recorded at
very low concentrations was enlarged and presented as an insert in
Fig. 6A. Fig. 6B presents the calibration plot of the amperometric
current response versus the acetaminophen concentration, show-
20 mVs-1 ing a good linear relationship in the tested acetaminophen
concentration range, with a correlation coefficient of R2 = 0.986.

10 The limit of detection (LOD) was calculated as described previous

in section 3.3. The LOD obtained through amperometry was
0 2.13 nM. The performance of different electrochemical sensors for
acetaminophen detection reported in the literature is compared in
-10 Table 1, showing that the ERG/GCE developed in the present study
exhibited a much lower LOD, as well as a much wider linear range.
-20
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7

E vs (Ag/AgCl) / V
40 25
B b
R2 = 0.999
30 c
I pa 20

20
15
I / μΑ

I / μA

10 a
10
0
I pc
2
R = 0.998
-10 5

-20 0
4 5 6 7 8 9 10 11 12 0.0 0.1 0.2 0.3 0.4 0.5 0.6

v1/2 / (mV s-1)1/2 E vs (Ag/AgCl) / V

Fig. 3. (A) CVs of the ERG/GCE recorded in 0.1 M PBS (pH 7.4) containing 250 mM Fig. 4. DPVs of the GCE modified with two-cycle (a), five-cycle (b) and ten-cycle (c)
acetaminophen at different scan rates varied from 20 to 125 mV s 1; (B) Plots of the electrodeposition of graphene measured in 0.1 M PBS (pH 7.4) containing 250 mM
anodic and cathodic peak currents versus the square root of the scan rates. acetaminophen.
202 B.-R. Adhikari et al. / Electrochimica Acta 162 (2015) 198–204

0.6
14 A A
800 μM 0.5
12
45 μM

10 0.4

I / μA
I / μΑ

5 μM 0.3
8 100 μM

5nM
6 0.2

4 0.1
2μΜ
2 0.0 0.2μM

0
0 200 400 600 800
0.2 0.3 0.4 0.5
t/s
E vs (Ag/AgCl) / V

14 B 0.5 B
12 R2= 0.986
0.4
10 R2 = 0.996
I / μΑ

I / μΑ
0.3
8

6 0.2

4
0.1
2

0.0
0 200 400 600 800 0 1000 2000 3000 4000
Concentration / μmol L-1 Concentration / nmol L -1

Fig. 5. (A) DPVs of the ERG/GCE recorded in 0.1 M PBS (pH 7.4) containing different
Fig. 6. (A) Amperometric current responses of the ERG/GCE as a result of the
acetaminophen concentrations (5 to 800 mM). For clarification, the inset is the
successive addition of acetaminophen at the increments of 5 nM, 0.2 mM and 2 mM
amplified DPV responses to acetaminophen at the low concentrations (5–45 mM)
at the electrode potential of 0.5 V in 0.1 M PBS (pH 7.4). The inset is the amplified
marked by the black rectangle; (B) the calibration plot of the current response
amperometric responses to acetaminophen at the low concentrations (5–25 nM)
against acetaminophen concentrations varied from 5 to 800 mM.
marked by the black rectangle; (B) the calibration plot of the current responses
against the acetaminophen concentration varied from 5 to 4000 nM.
3.5. Interference studies

The selective capability of the fabricated ERG/GCE sensor was

investigated via the detection of acetaminophen, as well as a
number of potential co-existing electroactive species, such as
ascorbic acid, uric acid, adenine, glucose and sucrose in a 0.1 M PBS
(pH 7.4). To facilitate the evaluation of the selective detection of
acetaminophen, Fig. 7A presents the DPVs of the ERG/GCE in 0.1 M
PBS + 20.0 mM acetaminophen in the absence of any interferents
(a) and in the presence of 40 mM ascorbic acid (b), 40 mM uric acid
(c), 40 mM adenine (d), 40 mM glucose (e), 40 mM sucrose (f) and
the mixture of all these biomolecules with 40 mM each (g). The DPV
response of the ERG/GCE to 20 mM acetaminophen generated an
anodic peak current of 0.72 mA as seen in Curve a of Fig. 7A. After
the addition of the interferents (Curve b–f) as well as their mixture
(Curve g), no obvious change of the peak potential and peak current
was observed. Fig. 7B, derived from Fig. 7A, presents the relative
anodic peak current responses to acetaminophen in the absence
and in the presence of the interferents. Less than 3% of the peak
current variation was observed for the detection of acetaminophen
at the ERG/GCE, demonstrating very high selectivity.
3.6. Reproducibility and stability of ERG/GCE sensor
The reproducibility and stability of the ERG/GCE were
investigated utilizing the DPV technique. To investigate the
reproducibility of the modified electrode, four different ERG/GCEs
were prepared under the same conditions, and tested for the
electrochemical detection of 250 mM acetaminophen in 0.1 M PBS.
A relative standard deviation of 0.78% was achieved with the
four different electrodes, confirming that the preparation of the
ERG/GCE had excellent reproducibility. One of the four ERG/GCEs
was selected for the further stability tests. The electrochemical
measurement with 0.1 M PBS containing 250 mM acetaminophen
was carried out once a day for seven days. The ERG/GCE was stored
in pure water when it was not in use. A relative standard deviation
of 7.07% was found, showing the high stability of the ERG/GCE for
the detection of acetaminophen.
3.7. Detection of acetaminophen in actual samples
To validate the practical application of the proposed sensor, the
fabricated ERG/GCE was employed to determine the concentration
of acetaminophen within an actual sample of acetaminophen
tablets in human serum. The recovery tests of acetaminophen were
carried out using DPV and the details were clearly described in the
experimental section. Recovery studies were carried out subse-
quently to the addition of a known volume of acetaminophen
tablets (325 mg) to the human serum plasma. As depicted in
Table 2, the proposed sensor exhibited an excellent recovery of
from 96.08% to 103.2%.
 B.-R. Adhikari et al. / Electrochimica Acta 162 (2015) 198–204 203

Table 1
Comparison of the recently reported electrochemical sensors for acetaminophen.

Modified electrodes pH Analytical methods Detection limit (mM) Linear range (mM) Reference
ERG/Ni2O3-NiO/GCE 7.0 DPV 0.02 0.04–100 39
SWCNT-GNS/GCE 7.0 DPV 0.038 0.05–64.5 42
Graphene/GCE 9.3 SWV 0.032 0.1–20 43
GRPE 8.5 SWV 0.60 2.5–143 44
Nafion/TiO2-GR/GCE 7.0 DPV 0.21 1–20 45
Fe3O4-PDDA-G/GCE 7.0 DPV 0.037 0.1–100 46
ERG/GCE 7.4 Amperometry/DPV 0.0021/1.2 0.005–4/5-800 This work

4. Conclusions

A In summary, an electrochemical sensor based on electrochemi-

0.5 μA
g cally reduced graphene was successfully fabricated for the
detection of acetaminophen. The developed ERG/GCE sensor
f demonstrated excellent electrocatalytic activity toward the
oxidation and reduction of acetaminophen. The sensor exhibited
I / μΑ

e high stability, good reproducibility and exclusive selectivity for the

detection of acetaminophen in the presence of other biomolecules.
d
The newly fabricated sensor was also studied with generic
c acetaminophen tablet concentrations in human serum plasma,
b further demonstrating its capabilities in practical medical appli-
cations. The proposed ERG/GCE sensor exhibited a much lower
a detection limit and a far wider linear detection range in contrast to
other electrochemical sensors reported in the literature. It
demonstrated strong potential for applications in the quality
0.0 0.1 0.2 0.3 0.4 0.5 0.6 control testing of pharmaceutical products, as well as hepatotox-
icity monitoring in hospitals and clinical laboratories.
E vs (Ag/AgCl) / V
120 Acknowledgements
B
This work was supported by a Discovery Grant from the Natural
100 Sciences and Engineering Research Council of Canada (NSERC). A.
C. acknowledges NSERC and the Canada Foundation for Innovation
80 (CFI) for the Canada Research Chair Award in Materials &
Environmental Chemistry.
I / I0

60
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